FDA-Led Research Team Discovers An Autoimmune Mechanism for Serious Drug-Induced Adverse Reactions

A team of researchers led by the U.S. Food and Drug
Administration has discovered a new mechanism for identifying and
understanding drug-related autoimmune reactions.

In an article available online today in the journal AIDS1
2, the team found that in certain at-risk patients, the
anti-HIV drug Ziagen (abacavir) causes the immune system to
“see” a patient’s own healthy tissues and
proteins as a foreign invader. The effect is similar to what
happens when the immune system recognizes a viral or bacterial
protein during an infection.

Abacavir is known to cause allergic reactions in certain,
at-risk patients. These reactions can range from mild skin
reactions to severe allergic shock and even death.

Abacavir interacts with molecules in the immune system called
Human Leukocyte Antigens (HLAs), specifically HLA-B*5701, which
help the body to distinguish “self” versus
“foreign” proteins. The drug can cause HLA-B*5701 to
present for the first time certain “self” proteins that
the body has not seen before. Because the body has not previously
recognized these “self” proteins, it mistakenly treats
them as foreign, resulting in the body trying to destroy its own
tissues. HLA-B*5701 is known to be a risk factor for serious
reactions to abacavir.

“This discovery is a new step towards understanding how
and why certain drugs cause severe allergic reactions in some
patients,” said Janet Woodcock, M.D., director of FDA’s
Center for Drug Evaluation and Research (CDER). “We hope
that, in the future, health care professionals will be able to
identify people who are at high risk of developing serious
reactions to various drugs, and offer them alternative
treatments.”

The research team’s work will provide the FDA with new
tools to analyze the safety of drugs that have the potential to
cause severe allergic reactions. This latest discovery will advance
the FDA’s ability to approve therapies that are personalized
for safety.

The results also may give biopharmaceutical companies and other
research organizations new methods to identify early in the
development process drugs with the potential to cause severe
adverse drug reactions. This may also serve as a model for future
research to predict drug reactions in different populations of
at-risk patients.

The research team was led by Michael Norcross, M.D., of the
Office of Pharmaceutical Sciences in CDER.

The FDA, an agency within the U.S. Department of Health and
Human Services, protects the public health by assuring the safety,
effectiveness, and security of human and veterinary drugs, vaccines
and other biological products for human use, and medical devices.
The agency also is responsible for the safety and security of our
nation’s food supply, cosmetics, dietary supplements,
products that give off electronic radiation, and for regulating
tobacco products.